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传染性 SARS-CoV-2 B.1.1.7 和 B.1.351 变体对中和抗体的敏感性。

Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies.

机构信息

Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.

CNRS UMR 3569, Paris, France.

出版信息

Nat Med. 2021 May;27(5):917-924. doi: 10.1038/s41591-021-01318-5. Epub 2021 Mar 26.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.

摘要

严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)的 B.1.1.7 和 B.1.351 变体分别在英国和南非首次被发现,此后已传播到许多国家。这些变体在编码刺突蛋白的基因中携带多种突变,这引起了人们对其免疫逃逸潜力的高度关注。在这里,我们从急性感染的个体中分离出了具有传染性的 B.1.1.7 和 B.1.351 株。我们比较了这两种变体对来自先前流行株感染或最近接种疫苗的个体血清和鼻腔拭子中 SARS-CoV-2 抗体的敏感性,与 D614G 参考病毒相比。我们利用了一种新的快速中和测定法,基于在过夜感染后对 GFP 呈阳性的报告细胞。从症状出现后 9 个月内采集的 58 名恢复期个体的血清,同样中和了 B.1.1.7 和 D614G。相比之下,9 个月后,恢复期血清的中和滴度平均降低了 6 倍,40%的样本对 B.1.351 缺乏任何活性。对 19 名接受过两次辉瑞公司 Cominarty 疫苗接种的个体进行纵向测试,结果表明,在接种后长达 6 周内,这些个体的血清对 B.1.1.7 同样有效,但对 B.1.351 的效果不如 D614G。第二次接种疫苗后,中和滴度增加,但对 B.1.351 的滴度仍低 14 倍。相比之下,恢复期或接种疫苗个体的血清在基于流式细胞术的血清学测定中同样结合了三种刺突蛋白。在疫苗接种者的鼻腔拭子中很少检测到中和抗体。因此,传播速度更快的 SARS-CoV-2 变体对自然感染或接种疫苗产生的中和抗体获得了部分耐药性,这种耐药性在抗体水平较低的个体中最常被检测到。我们的结果表明,B1.351 可能会增加免疫个体感染的风险,但 B.1.1.7 不会。

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